PROJECT SUMMARY (PUBLIC ABSTRACT) The natural lower limbs provide important biomechanical functions such as body weight support, forward propulsion, and balance control during ambulation. When the loads borne by the lower limbs change, lower limb muscle activation responds accordingly to enable seamless continuation of biomechanical function. These loads can change suddenly, such as when carrying an infant, toddler, or other load like a heavy backpack. For individuals with a lower limb amputation, these sudden changes to weight-bearing loads can be problematic because they can negatively impact walking performance. One reason walking performance may suffer is that the properties of most prosthetic limbs, such as their stiffness, are constant and do not change to suit varying load conditions. Another reason is that the most widely prescribed prosthetic feet do not have motors, sensors, or brain-like controllers that act to replace the neuromuscular system of the amputated limb. Regardless of the reason, no evidence exists to guide prescription practice for veterans who walk with a prosthesis and experience sudden load changes. The proposed research will use experimental and modeling analyses to create guidance for VA clinicians who prescribe prostheses to veterans with a lower limb amputation who frequently carry infants, toddlers or other loads. Our proposed research has two specific aims: Specific Aim 1: Identify the prosthetic foot that results in improved walking performance when veterans with lower limb amputation carry infants, toddlers, or other loads. We propose to conduct a human subject experiment with help of fifteen individuals with below-knee amputations. Study participants will walk on a treadmill with no added load and four added load conditions using a weighted pack (13.6 kg or ~30 lbs) to simulate an infant, toddler, or other load. The four conditions include the pack strapped to their front, their back, and carried with their arms on the intact limb side and the prosthetic limb side. Each participant will wear a usual prosthetic foot, this same foot with a heel-stiffening wedge, the same prosthetic foot but one category stiffness higher, a new-to-market dual keel prosthetic foot intended for load carrying situations, and a powered ankle foot prosthesis. The results from these experiments will aid VA clinicians in specifying the best prosthesis for veterans with lower limb amputations who frequently carry infants, toddlers, or other loads. Specific Aim 2: Identify the sensitivity of muscle contributions to specific biomechanical quantities in response to the different stiffness and loading conditions. We propose to use advanced modeling and simulation analyses to identify how foot stiffness influences individual muscle contributions to specific biomechanical quantities including body weight support, forward propulsion, balance control, energy expenditure, and joint loading for the different loading conditions examined in Aim 1. We will further perform exploratory analyses with increased weight increments to discover the sensitivity of muscle contributions to the biomechanical quantities. We anticipate these results will provide significant insight into these relationships because with our model we can explore a much wider range of conditions than we can using experimental methods and volunteer participants. For veterans who wear a lower limb prosthesis while carrying infants, toddlers, or other loads, this research will provide evidence to support prosthesis prescription practice that reduces undesirable compensatory responses to load carriage. Our objective is to help clinicians select among currently available solutions to enable veterans to achieve their life and work goals.